New ways of measuring blood-to-brain transfer constants for materials of low to moderate blood-brain barrier (BBB) permeability, of obtaining multiple blood samples from small animals without changes in blood pressure and flow, and of making double label (14C plus 111In or 14C plus 125I) quantitative autoradiographic measurements were developed. An intraventricular Walker 256 brain tumor model was set up. Marked increases in blood-tissue transfer of alpha-aminoisobutyric acid (AIB) were observed in this lesion when the tumor reached a size of about 0.2mm. In work with a different metastatic Walker 256 brain tumor model, it was shown that glucose utilization was low in the core of the tumor and "normal" tissue adjacent to the tumor but very high at the periphery of the tumor, that blood flow was lower than normal throughout the tumor, and that BBB permeability to AIB was sharply increased in the larger tumor masses. Blood-brain-CSF distribution studies of antitumor and radiopharmaceutical agents indicated that brain and CSF uptakes of methotrexate (high dose), metrizamide, and diatrozoate were very slow, that thymidine and thymine transfer from blood to CSF occurred at moderate rates, and that spirohydantoin mustard rapidly crossed the BBB and entered brain cells.